Abstract

Somatic mosaicism, the occurrence and propagation of genetic variation in cell lineages after fertilization, is increasingly recognized to play a causal role in a variety of human diseases. We investigated the case of life-threatening arrhythmia in a 10-day-old infant with long QT syndrome (LQTS). Rapid genome sequencing suggested a variant in the sodium channel NaV1.5 encoded by SCN5A, NM_000335:c.5284G > T predicting p.(V1762L), but read depth was insufficient to be diagnostic. Exome sequencing of the trio confirmed read ratios inconsistent with Mendelian inheritance only in the proband. Genotyping of single circulating leukocytes demonstrated the mutation in the genomes of 8% of patient cells, and RNA sequencing of cardiac tissue from the infant confirmed the expression of the mutant allele at mosaic ratios. Heterologous expression of the mutant channel revealed significantly delayed sodium current with a dominant negative effect. To investigate the mechanism by which mosaicism might cause arrhythmia, we built a finite element simulation model incorporating Purkinje fiber activation. This model confirmed the pathogenic consequences of cardiac cellular mosaicism and, under the presenting conditions of this case, recapitulated 2:1 AV block and arrhythmia. To investigate the extent to which mosaicism might explain undiagnosed arrhythmia, we studied 7,500 affected probands undergoing commercial gene-panel testing. Four individuals with pathogenic variants arising from early somatic mutation events were found. Here we establish cardiac mosaicism as a causal mechanism for LQTS and present methods by which the general phenomenon, likely to be relevant for all genetic diseases, can be detected through single-cell analysis and next-generation sequencing.

Abstract

Combined heart and liver transplantation (CHLT) in the pediatric population involves a complex group of patients, many of whom have palliated congenital heart disease (CHD) involving single ventricle physiology.The purpose of this study was to describe the perioperative management of pediatric patients undergoing CHLT at a single institution and to identify management strategies that may be used to optimize perioperative care.We did a retrospective database review of all patients receiving CHLT at a children's hospital between 2006 and 2014. Information collected included preoperative characteristics, intraoperative management, blood transfusions, and postoperative morbidity and mortality.Five pediatric CHLTs were performed over an 8-year period. All patients had a history of complex CHD with multiple sternotomies, three of whom had failing Fontan physiology. Patient age ranged from 7 to 23 years and weight from 29.5 to 68.5 kg. All CHLTs were performed using an en-bloc technique where both the donor heart and liver were implanted together on cardiopulmonary bypass (CPB). The median operating room time was 14.25 h, median CPB time was 3.58 h, and median donor ischemia time was 4.13 h. Patients separated from CPB on dopamine, epinephrine, and milrinone infusions and two required inhaled nitric oxide. All patients received a massive intraoperative blood transfusion post CPB with amounts ranging from one to three times the patient's estimated blood volume. The patient who required the most transfusions was in decompensated heart and liver failure preoperatively. Four of the five patients received an antifibrinolytic agent as well as a procoagulant (prothrombin complex concentrate or recombinant activated Factor VII) to assist with hemostasis. There were no 30-day thromboembolic events detected. Postoperatively the median length of mechanical ventilation, ICU stay and stay to hospital discharge was 4, 8, and 37 days, respectively. All patients are alive and free from allograft rejection at this time.Combined heart and liver transplantation in the pediatric population involves a complex group of patients with unique perioperative challenges. Successful management starts with thorough preoperative planning and communication and involves strategies to deal with massive intraoperative hemorrhage and coagulopathy in addition to protecting and supporting the transplanted heart and liver and meticulous surgical technique. An integrated multidisciplinary team approach is the cornerstone for successful outcomes.

Abstract

Despite increasing use of mechanical circulatory support in children, experience with biventricular device implantation remains limited. We describe our experience using the HeartWare HVAD to provide biventricular support to 3 patients and compare these patients with 5 patients supported with HeartWare LVAD. At the end of the study period, all three BiVAD patients had been transplanted and were alive. LVAD patients were out of bed and ambulating a median of 10.5 days post implantation. The BiVAD patients were out of bed a median of 31 days post implantation. Pediatric patients with both left ventricular and biventricular heart failure can be successfully bridged to transplantation with the HeartWare HVAD. Rapid improvement in functional status following HVAD implantation for isolated left ventricular support is seen. Patients supported with BiVAD also demonstrate functional recovery, albeit more modestly. In the absence of infection, systemic inflammatory response raises concern for inadequate support.

Abstract

Acute kidney injury (AKI) is common in children following surgery for congenital heart disease and has been associated with poor long-term kidney outcomes. Children undergoing heart transplantation may be at increased risk for the development of both AKI and chronic kidney disease (CKD). This study examines AKI rates in children, adolescents, and young adults after heart transplantation and analyzes the relationship between AKI and CKD in this population.Retrospective cohort study.88 young patients who underwent heart transplantation at Lucile Packard Children'sHospital, Stanford, CA, September 1, 2007, to November 30,2013.The primary independent variable was AKI within the first 7 postoperative days, ascertained according to the KDIGO (Kidney Disease: Improving Global Outcomes) creatinine criteria (increase in serum creatinine 1.5 times baseline within 7 days).Recovery from AKI at 3 months, ascertained as serum creatinine level< 1.5 times baseline; and development of CKD at 6 and 12 months, ascertained as estimated glomerular filtration rate< 60mL/min/1.73m(2) for more than 3 months.63 (72%) patients developed AKI; 57% had moderate (stage 2 or severe stage 3) disease. Recoveryoccurred in 39 of 63 (62%), 50% for stage 2 or 3 versus 78% for stage 1 (P=0.04). At 6 and 12 months, 3 of 82 (4%) and 4 of 76 (5%) developed CKD, respectively. At both time points, CKD was more common in those without recovery (3/22 [14%] vs 0/38 (0%); P=0.04, and 3/17 (18%) vs (0/34) 0%; P=0.03, respectively).Retrospective design, small sample size, and single-center nature of the study.AKI is common after heart transplantation in children, adolescents, and young adults. Nonrecovery from AKI is more common in patients with more severe AKI and is associated with the development of CKD during the first year.

Abstract

Pediatric patients with end-stage respiratory failure and pulmonary hypertension traditionally have poor outcomes when bridged with extracorporeal membrane oxygenation to lung or heart-lung transplantation. Therefore, several institutions have attempted paracorporeal lung assist devices as a bridge. However, given the small number of patients, little is known about approaches to anesthetic induction in these hemodynamically unstable patients either before placement of a device or anesthetic induction once a device is in situ. In this case report, we describe our anesthetic experience managing a 13-year-old boy for both paracorporeal lung assist device placement and subsequent heart-lung transplantation.

Abstract

Although ventricular assist devices (VADs) restore hemodynamics in those with heart failure, reversibility of end-organ dysfunction with VAD support is not well characterized. Renal function often improves in adults after VAD placement, but this has not been comprehensively explored in children.Sixty-three children on VAD support were studied. Acute kidney injury (AKI) was defined by Kidney Disease: Improving Global Outcomes criteria. Estimated glomerular filtration rate (eGFR) was determined by the Schwartz method. Generalized linear mixed-effects models compared the pre-VAD and post-VAD eGFR for the cohort and sub-groups with and without pre-VAD renal dysfunction (pre-VAD eGFR < 90 ml/min/1.73 m(2)).The pre-VAD eGFR across the cohort was 84.0 ml/min/1.73 m(2) (interquartile range [IQR] 62.3-122.7), and 55.6% (34 of 63) had pre-VAD renal dysfunction. AKI affected 60.3% (38 of 63), with similar rates in those with and without pre-existing renal dysfunction. Within the cohort, the nadir eGFR occurred 1 day post-operatively (62.9 ml/min/1.73 m(2); IQR, 51.2-88.9 ml/min/1.73 m(2); p < 0.001). By Day 5, however, the eGFR exceeded the baseline (99.0 ml/min/1.73 m(2); IQR, 59.3-146.7 ml/min/1.73 m(2); p = 0.03) and remained significantly higher through the first post-operative week. After adjusting for age, gender, and AKI, the eGFR continued to increase throughout the entire 180-day study period ( = 0.0025; 95% confidence interval, 0.0015-0.0036; p < 0.001). Patients with pre-VAD renal dysfunction experienced the greatest improvement in the eGFR ( = 0.0051 vs = 0.0013, p < 0.001).Renal dysfunction is prevalent in children with heart failure undergoing VAD placement. Although peri-operative AKI is common, renal function improves substantially in the first post-operative week and for months thereafter. This is particularly pronounced in those with pre-VAD renal impairment, suggesting that VADs may facilitate recovery and maintenance of kidney function in children with advanced heart failure.

Abstract

In neonates, it is challenging to diagnose aortic coarctation in the setting of a patent ductus arteriosus (PDA). Frequently, serial echocardiograms are performed, and diagnosis is delayed until the PDA closes. The purpose of this study was to identify echocardiographic predictors of neonatal coarctation in the presence of a PDA in cases in which diagnosis is uncertain.We retrospectively identified neonates diagnosed with possible but not definitive coarctation in the presence of a PDA by echocardiography (January 2004 through August 2013). The carotid-subclavian artery index (CSAi) was defined as the distal transverse arch diameter divided by the distance between the left common carotid and left subclavian arteries. Medical records were reviewed to identify patients who underwent coarctation repair within 1 year. A separate validation group was identified with the same methodology (September 2013 through April 2015).Thirty-three patients were identified (median age 1, range 0-8 days). Twelve patients (36%) underwent coarctation repair. The coarctation group had smaller aortic and mitral valves, distal transverse arch, and isthmus z scores, larger right innominate artery, and longer transverse arch compared with the remaining group (p < 0.05). The CSAi was lower in the coarctation group (p = 0.014), and a cutoff of less than 0.85 yielded a sensitivity of 0.83and specificity of 0.86 for coarctation (area under the receiver operating characteristic curve, 0.91). In the validation group (n= 12; median follow-up, 316 days), none of the 8 patients with a CSAi of greater than 0.85 have required surgery. The intraclass correlation coefficient for CSAi was 0.79 (95% confidence interval, 0.18 to 0.95).The CSAi, a simple and reproducible measure, can identify neonates at risk for aortic coarctation even in the presence of a PDA, prevent multiple echocardiographic evaluations, and hence guide appropriate resource utilization.

Abstract

Outpatient experience of children supported with continuous flow ventricular assist devices (CFVAD) is limited. We reviewed our experience with children discharged with CF-VAD support.All pediatric patients <18 years old with CF-VADs implanted at our institution were included. Discharge criteria included a stable medication regimen, completion of a VAD education program and standardized rehabilitation plan, and presence of a caregiver. Hospital re-admissions (excluding scheduled admissions) were reviewed. Adverse events were defined by INTERMACS criteria.Of 17 patients with CF-VADs, 8(47%) were discharged from the hospital (1 Heartware HVAD, 7 Heartmate II). Median age was 15.3(range 9.6-17.1) years and weight was 50.6(33.6-141) kg. Device strategies were destination therapy (n=4) and bridge to transplant (n=4). Patients spent a median 49(26-107) days hospitalized post-implant and had 2(1-5) hospital re-admissions. Total support duration was 3154 patient-days, with 2413 as outpatient. Most frequent adverse events were device malfunction and arrhythmias. There was one death due to pump thrombosis, and no bleeding or stroke events. Overall adverse event rate was 15.22 per 100-patient-months.Early experience suggests that children with CF-VADs can be safely discharged. Device malfunction and arrhythmia were the most common adverse events but were recognized quickly with structured outpatient surveillance.

Abstract

Aortic valve (AV) disease presents critical situations requiring surgery in over 2% of the US population and is increasingly the reason for cardiac surgery. Throughout the AV cycle, mechanical forces of multiple types and varying intensities are exerted on valve leaflets. The mechanisms whereby forces regulate leaflet homeostasis are incompletely understood. We used a novel flow bioreactor culture to investigate alteration of AV opening or closure on leaflet genes.Culture of rat AV was conducted in a flow bioreactor for 7days at 37C under conditions approximating the normal stroke volume. Three force condition groups were compared: Cycling (n=8); always open (Open; n=3); or always closed (Closed; n=5). From each culture, AV leaflets were pooled by force condition and RNA expression evaluated using microarrays. Hierarchical clustering of 16 transcriptome data sets from the 3 groups revealed only 2 patterns of gene expression: Cycling and Closed groups clustered together, whereas Open AV were different (P<0.05). Sustained AV opening induced marked changes in expression (202 transcripts >2-fold; P<0.05), whereas Closed AV exhibited similar expression pattern as Cycling (no transcripts >2-fold; P<0.05). Comparison with human sclerotic and calcific AV transcriptomes demonstrated high concordance of >40 Open group genes with progression toward disease.Failure of AV to close initiates an extensive response characterized by expression changes common to progression to calcific aortic valve disease. AV coaptation, whether phasic or chronic, preserved phenotypic gene expression. These results demonstrate, for the first time, that coaptation of valve leaflets is a fundamentally important biomechanical cue driving homeostasis.

Abstract

Limited availability of donor organs has led to the use of ventricular assist devices (VADs) to treat heart failure in pediatric patients, primarily as bridge to transplantation. How effective VAD therapy is in promoting functional recovery in children is currently not known.We report morbidity and mortality as defined by the Interagency Registry for Mechanically Assisted Circulatory Support Modified for Pediatrics (PediMACS) and the use of the Treatment Intensity Score to assess functional status for 50 VAD patients supported at a single pediatric program from 2004 to 2013.In this cohort, 30-day survival on VAD was 98%, and 180-day survival was 83%. Stroke occurred in 11 patients (22%), with 8 (16%) resulting in persistent neurologic deficit or death. The adverse event rate was 2-fold to 3-fold higher in the first 7 days of support compared with the subsequent support period. Functional status, as measured by the Treatment Intensity Score, improved with duration of support. Successful bridge to transplantation was associated with fewer adverse events during support and greater improvement in the Treatment Intensity Score during the period of support.Overall survival in this cohort is excellent. The risk of serious adverse events decreases over the first month of support. However, a clinically significant risk of morbidity and mortality persists for the duration of pediatric VAD support. Measures of functional status improve with duration of support and are associated with survival to transplantation.

Abstract

There are conflicting reports regarding the importance of mitral stenosis and aortic atresia as a risk factor for Norwood mortality. This study reviews outcomes of this anatomic subgroup at our institution and examines the utility of preoperative cardiac catheterization and its correlation with clinical outcomes and pathology findings.This is a single-center, retrospective review of hypoplastic left heart syndrome patients who underwent modified Norwood operation between October 2005 and May2013.Fourteen of 74 hypoplastic left heart syndrome patients (19%) had mitral stenosis and aortic atresia. Operative mortality for MS/AA was 29% versus 7% for all other hypoplastic left heart syndrome anatomic subgroups (p= 0.04). Although only 19% of the entire cohort, the mitral stenosis and aortic atresia subgroup constituted 50% of the total operative mortality and the only interstage deaths. Autopsies support myocardial ischemia as the mechanism of death. Although preoperative angiography defined the presence of ventriculo-coronary connections, it did not clearly risk stratify patients in regard to operative mortality.Mitral stenosis and aortic atresia is a risk factor for perioperative myocardial ischemia and mortality. Further exploration of myocardial reserve is warranted.

Abstract

Single-center data on pediatric heart transplantation spanning long time frames is sparse. We attempted to analyze how risk profile and pediatric heart transplant survival outcomes at a large center changed over time.We divided 320 pediatric heart transplants done at Stanford University between 1974 and 2014 into three groups by era: the first 20 years (95 transplants), the subsequent 10 years (87 transplants), and the most recent 10years (138 transplants). Differences in age at transplant, indication, mechanical support, and survival were analyzed.Follow-up was 100% complete. Average age at time of transplantation was 10.4 years, 11.9 years, and 5.6 years in eras 1, 2, and 3, respectively. The percentage of infants who received transplants by era was 21%, 7%, and 18%, respectively. The indication of end-stage congenital heart disease vs cardiomyopathy was 24%, 22%, and 49%, respectively. Only 1 patient (1%) was on mechanical support at transplant in era 1 compared with 15% in era 2 and 30% in era 3. Overall survival was 72% at 5 years and 57% at 10 years. Long-term survival increased significantly with each subsequent era. Patients with cardiomyopathy generally had a survival advantage over those with congenital heart disease.The risk profile of pediatric transplant patients in our institution has increased over time. In thelast 10 years, median age has decreased and ventricular assist device support has increased dramatically. Transplantation for end-stage congenital heart disease is increasingly common. Despite this, long-term survival has significantly and consistently improved.

Abstract

Durable mechanical support in situations of physiologic single ventricle has been met with little success so far, particularly in small children. We created an animal model to investigate whether pulsatile or continuous flow would be superior. Three 1 month old sheep (10-16kg) were instrumented. Via sternotomy and with cardiopulmonary bypass, a large ventricular septal defect and atrial septal defect were created. The left ventricle was cannulated using a Berlin Heart inflow cannula. This was connected sequentially to a continuous flow device (Thoratec HeartMate X, Pleasanton, CA) and to a pulsatile device (Berlin Heart Excor, The Woodlands, TX). Outflow was via a Y-graft to both aorta and pulmonary artery, striving for equal flow to both. Atrial filling pressures were controlled with volume infusions over a wide range. Under comparable loading conditions, significantly higher maximum flow was obtained by HeartMate X than by Excor (4.951.27L/min [range, 3.84-6.34L/min] for HeartMate X vs. 1.800.85L/min [range, 1.01-2.7L/min] for Excor; p < 0.05). Judging from this limited animal study, in single ventricle scenarios, continuous flow devices may achieve higher pump flows than pulsatile devices when provided with similar filling pressures. Their clinical use should be investigated. More extensive experimental studies are needed.

Abstract

Anomalous aortic origin of the left coronary artery is rare and confers increased risk of sudden cardiac death. Accurate diagnosis is crucial and often requires many diagnostic modalities. This case report highlights the echocardiographic characteristics and pitfalls in diagnosing the anomaly in addition to the advantages of using computed tomography and magnetic resonance imaging in a pediatric patient.

Abstract

The evolution of pharmacologic therapies and mechanical support including ventricular assist devices (VADs) has broadened the scope of care available to children with advanced heart failure. At the present time, there are only limited means of quantifying disease severity or the concomitant morbidity for this population. This study describes the development of a novel pediatric treatment intensity score (TIS), designed to quantify the burden of illness and clinical trajectory in children on VAD support.There were 5 clinical domains assessed: nutrition, respiratory support, activity level, cardiovascular medications, and care environment. A scale was developed through expert consensus. Higher scores indicate greater morbidity as reflected by intensity of medical management. To evaluate feasibility and face validity, the TIS was applied retrospectively to a subset of pediatric inpatients with VADs. The Bland-Altman method was used to assess limits of agreement.The study comprised 39 patients with 42 implantations. Bland-Altman interobserver and intraobserver comparisons showed good agreement (mean differences in scores of 0.02, limits of agreement 0.12). Trends in TIS were concordant with the overall clinical impression of improvement. Scores remained 0.6 preceding VAD implantation and peaked at 0.71 3 days after VAD implantation.We describe a pediatric VAD scoring tool, to assess global patient morbidity and clinical recovery. We demonstrate feasibility of using this TIS in a test population of inpatients on VAD support.

Abstract

Many children who undergo heart transplantation will survive into adulthood. We sought to examine the QOL and capacity for achievement in long-term adult survivors of pediatric heart transplantation. Adults >18yr of age who received transplants as children (18yr old) and had survived for at least 10yr post-transplant completed two self-report questionnaires: (i) Ferrans & Powers QLI, in which life satisfaction is reported as an overall score and in four subscale domains and is then indexed from 0 (very dissatisfied) to 1 (very satisfied); and (ii) a "Metrics of Life Achievement" questionnaire regarding income, education, relationships, housing status, and access to health care. A total of 20 subjects completed the survey. The overall mean QLI score was 0.770.16. Subjects were most satisfied in the family domain (0.840.21) and least satisfied in the psychological/spiritual domain (0.70.28). Satisfaction in the domains of health/functioning and socioeconomic were intermediate at 0.78 and 0.76, respectively. Most respondents had graduated from high school, reported a median annual income >$50000/yr, and lived independently. Adult survivors of pediatric heart transplant report a good QOL and demonstrate the ability to obtain an education, work, and live independently.

Abstract

It is recognized that there are numerous anatomic variants that result in hypoplastic left heart physiology. One such variant includes critical aortic stenosis or atresia, a hypoplastic aortic arch, and a reasonably well-developed left ventricle due to the presence of a ventricular septal defect. These patients are candidates for 1 of 3 surgical options: (1) a Norwood procedure followed by a single-ventricle pathway; (2) a Norwood procedure followed by a Rastelli procedure (2-stage Yasui); or (3) a single-stage Yasui procedure. Because 2 of the 3 options include a Norwood procedure as the initial step, the purpose of this study was to evaluate the contemporaneous results of the Yasui and Norwood procedures at a single institution.This was a retrospective review of patients who underwent a Yasui or Norwood procedure at Lucile Packard Children's Hospital between 2004 and 2013. Eighteen patients underwent a Yasui, of whom 15 had a single-stage procedure and 3 had a 2-stage procedure. During this time frame, 113 patients underwent a Norwood procedure. Kaplan-Meier survival curves and freedom from reoperation were compared for the 2 procedures.The operative mortality (using the Society of Thoracic Surgeons definition) for the single-stage Yasui was 6.7% compared with 16% for the Norwood procedure (P

Abstract

Children requiring a permanent epicardial pacemaker(PM) traditionally have a single lead placed on the right ventricle. Lead failure in pacemaker dependent(PMD) children, however, can result in cardiovascular events(CVE) and death.To determine if redundant ventricular lead systems(RVLS) can safeguard against CVE and death in PMD children.Single-center study of PMD patients undergoing placement of RVLS from 2002-2013. Patients 21 years of age who were PMD were included. Patients with biventricular systems(BiV) systems placed for standard resynchronization indications were excluded. RVLS patients were compared to PMD patients with only a single pacing lead on the ventricle(SiV).769 patients underwent PM/ICD placement with 76 BiV implants and there were 49 PMD patients(6%). 13 patients underwent implantation of a RVLS. There was no difference between the RVLS group(n=13) and SiV PMD control group(n=24) with regard to age(RVLS 9.55.8 vs. SiV 9.46.7 years; p=0.52), weight(RVLS 38.232.6 vs. SiV 35.229.3 kg; p=0.62), indication for pacing, procedural complications or time to follow-up. There were 2 lead fractures (17%) in the RVLS group(mean follow-up 3.82.9 years) with no deaths or presentations with CVE. The SiV control group had 3 lead fractures (13%)(mean follow-up 2.82.9 years), with no deaths, but all 3 patients presented with CVE and required emergent PM placement.RVLS systems should be considered in children who are PMD and require permanent epicardial pacing. BiV pacing and RVLS may decrease the risk of CVEs in the event of lead failure in PMD patients.

Abstract

The advent of clinical next generation sequencing is rapidly changing the landscape of rare disease medicine. Molecular diagnosis of long QT syndrome (LQTS) can impact clinical management, including risk stratification and selection of pharmacotherapy based on the type of ion channel affected, but results from current gene panel testing requires 4 to 16 weeks before return to clinicians.A term female infant presented with 2:1 atrioventricular block and ventricular arrhythmias consistent with perinatal LQTS, requiring aggressive treatment including epicardial pacemaker, and cardioverter-defibrillator implantation and sympathectomy on day of life two. We sought to provide a rapid molecular diagnosis for optimization of treatment strategies.We performed CLIA-certified rapid whole genome sequencing (WGS) with a speed-optimized bioinformatics platform to achieve molecular diagnosis at 10 days of life.We detected a known pathogenic variant in KCNH2 that was demonstrated to be paternally inherited by followup genotyping. The unbiased assessment of the entire catalog of human genes provided by whole genome sequencing revealed a maternally inherited variant of unknown significance in a novel gene.Rapid clinical WGS provides faster and more comprehensive diagnostic information by 10 days of life than standard gene-panel testing. In selected clinical scenarios such as perinatal LQTS, rapid WGS may be able to provide more timely and clinically actionable information than a standard commercial test.

Abstract

Tetralogy of Fallot patients with pulmonary atresia (TOF/PA) present a pulmonary blood supply directly from aortic collateral arteries. Major aorto-pulmonary collateral arteries (MAPCAs) present substantial clinical and surgical management challenges. Surgical operations to reestablish and promote further development of a pulmonary arterial connection preferentially utilize MAPCAs for reconstruction of central pulmonary arteries. However, the propensity of some MAPCAs to develop stenosis rather than growth may impair the response to reconstructions.Probe sets prepared from MAPCAs, PA, and aorta mRNA were used to interrogate human genome microarrays. We compared expression differences between pairs of the three vessels to determine whether MAPCAs display distinct expression patterns.Functional clustering analysis identified differences in gene expression, which were further analyzed by gene ontology classification. A subset of highly regulated genes was validated using quantitative PCR. Expression differences among vessel types were observed for multiple gene classes. Of note, we observed that MAPCAs differentially express several genes at much higher levels than either PA or aorta.MAPCAs differ from PA or aorta by significantly altered levels in gene expression, suggesting a transcriptional basis for their physiology that will guide a further understanding of the pathobiology of MAPCAs and TOF.

Abstract

Structured rehabilitation programs in adults after ventricular assist device (VAD) placement result in improvements in physical function and exercise capacity, and have been shown to improve survival and accelerate post-transplant recovery. The objective of this study was to determine the safety and feasibility of an acute inpatient rehabilitation program for children utilizing standardized, age-appropriate, family-centered care pathways after paracorporeal VAD placement in both the ICU and acute-care inpatient settings.Between November 12, 2010 and March 15, 2013, 17 patients were referred to therapy after VAD implantation, 14 of whom were medically stable enough to participate. Beginning in the ICU, a structured physical and occupational therapy program was implemented utilizing novel age-appropriate, standardized care pathways for infants (age <1 year) and children (age 1 to 12 years). The infant and child pathways consisted of 8 and 10 goals, respectively. Retrospective review was conducted to ascertain the number of phases achieved per patient. Adverse events, defined as bleeding, physiologic instability, stroke, or device disruption during therapy, were also analyzed.The median age was 1.1 (range 0.5 to 14.4) years in the 14 patients considered medically stable enough to participate in rehabilitation. Nine of them were female. Eight patients participated in the infant standardized care pathway (SCP) and 6 participated in the child SCP. Seven patients were on biventricular support. Twelve patients were transplanted and survived. Two patients died while awaiting transplantation. There were 1,473 total days on the VAD (range 40 to 229 days). The median time to extubation was 2 days (range 1 to 8) and the median ICU stay was 6.5 days (range 3 to 152). Eleven patients achieved all goals of the SCP, including all of the patients in the child group. For the infant group, 5 patients achieved all goals of the SCP (range 5 to 8), and all but 1 patient achieved at least 7 goals of the SCP. There were no adverse events related to therapy.Standardized, family-centered inpatient rehabilitation care paths are safe for infants and children after paracorporeal device placement. Structured rehabilitation goals can be achieved by the majority of pediatric patients during VAD support. Early mobilization and inpatient rehabilitation in this cohort promotes normalization of function while awaiting cardiac transplantation.

Abstract

Ventricular assist devices are frequently used to bridge pediatric patients to cardiac transplantation; however, experience in single ventricle patients with aortopulmonary shunts remains limited. This case report addresses the challenge of balancing pulmonary and systemic circulation with a focus on the role of continuous versus pulsatile ventricular assist device support.

Abstract

The relationship between SES and outcomes surrounding pediatric cardiac transplantation is complex and influenced by recipient race. Broad-based studies of SES have not been performed. A retrospective review of all 5125 primary pediatric heart transplants performed in the United States between 2000 and 2011. Patients were stratified by SES based on zip code of residence and U.S. census data (low SES: 1637; mid-SES: 2253; high SES: 1235). Survival following listing and transplantation was compared across strata. Risk-adjusted long-term mortality on the waitlist was higher among low SES patients (hazard 1.32, CI 1.07-1.63). The relationship between SES and outcomes varied by race. Early risk-adjusted post-transplant outcomes were worst among high SES patients (10.8% vs. low SES: 8.9%, p<0.05). The incidence of non-compliance was higher among low SES patients (p<0.0001). Long-term risk-adjusted patient survival was poorer among low (hazard 1.41, CI 1.10-1.80) and mid-SES (1.29, 1.04-1.59) groups. Low SES is associated with worse outcomes on both the waitlist and late following transplantation. Higher SES patients had more complex transplants with higher early mortality. Further research should be directed at identifying and addressing underlying causal factors for these disparities.

Abstract

Fetal cardiac surgery is a potential innovative treatment for certain congenital heart defects that have significant mortality and morbidity in utero or after birth, but it has been limited by placental dysfunction after fetal cardiac bypass. We have used the TinyPump device for fetal cardiac bypass in sheep fetuses at 90 to 110days gestation.Ten mixed-breed pregnant ewes were used over a period of 6 months, and 10 fetuses were placed on bypass for 30 minutes. Five fetuses with a mean gestational age of 104 4.5 days and mean weight of 1.4 0.4 kg were placed on bypass using the TinyPump device, and 5 fetuses with a mean gestational age of 119 4.5 days and mean weight of 3.4 0.4 kg were placed on bypass using the roller head pump. The fetuses were monitored for up to 3 hours after bypass or until earlier demise.Progressive respiratory and metabolic acidosis developed in all fetuses. The TinyPump group had a lower gestational age and weight compared with the roller head pump group. However, the rate of postbypass deterioration in the TinyPump group, as measured with blood gases, was noted to be significantly slower compared with the roller head pump group.We demonstrate the feasibility of the TinyPump device for fetal cardiac bypass in a fetal sheep model. The TinyPump group showed improved results compared with the roller head group despite more immature fetuses. The TinyPump device seems to be a promising device for future studies of fetal cardiac bypass in immature fetal sheep and in primates.

Abstract

For patients with end-stage hepatic failure secondary to failing hemodynamics, combined heart-liver transplant (H-LT) remains the only option for long-term survival. We report a series of three pediatric patients who successfully underwent orthotopic H-LT for failed single-ventricle palliation. All three patients are currently living, now two, three, and five years post-transplant, and remain completely free of cardiac cellular allograft rejection despite reduced immunosuppression protocols. One patient, however, did develop acute antibody-mediated rejection in the immediate post-transplant period, suggesting that this protective effect may be less effective in attenuating humoral mechanisms of rejection.

Abstract

The management of congenital aortic stenosis in neonates and infants continues to be a surgical challenge. We have performed the modified Ross-Konno procedure for patients who have severe aortic insufficiency or significant residual stenosis after balloon aortic dilation. The midterm results of this procedure were evaluated in this subset of patients.Between 1994 and 2010, a total of 24 patients younger than 1 year of age underwent the modified Ross-Konno procedure. The diagnoses were aortic stenosis with or without subaortic stenosis (n = 16), Shone's complex (n = 7), and interrupted aortic arch with subaortic stenosis (n = 1). The aortic root was replaced with a pulmonary autograft, and the left ventricular outflow tract (LVOT) was enlarged with a right ventricular infundibular free wall muscular extension harvested with the autograft.Age at operation ranged from 1 to 236 days (median 28 days). The median follow-up period was 81 months (range 1-173 months). There was 1 early death and no late mortality. Overall the 1-, 2-, and 5-year survival rate was 95% 4.5%. Freedom from aortic stenosis was 94.7% 5.1% at 1, 2, and 5 years. Less than mild aortic insufficiency was 93.3% 6.4% at 2 years, and 74.7% 12.9% at 5 years. In total, 23 reoperations and reinterventions were performed; 14 were allograft conduit replacements. Two patients required aortic valve plasty. None required valve replacement. The reintervention-free rate was 64.6% 10.8% at 2 years and 36.9% 11.3% at 5 years.Pulmonary autografts demonstrated good durability with low mortality and morbidity. This study shows that the modified Ross-Konno procedure can be a practical choice in selective cases for complex LVOT stenosis in neonates and infants.

Abstract

Pediatric CHLT is rarely performed in transplant centers and even fewer are performed en bloc. In the hands of an experienced surgeon with the appropriate patient selection, CHLT performed en bloc may have several operative and immunologic benefits, thereby resulting in improved outcomes for the transplant recipient. A single-institutional, retrospective review from 1/1/06 to 12/31/10 was conducted. Three pediatric patients with end-stage heart and liver disease who were considered low immunologic risk were included. All were managed by the same surgeon with a herein-described CHLT donor and recipient operation. Data were collected on patient and graft survival, rejection episodes, infectious complications, operative time, intraoperative transfusion requirements, and immunosuppression regimens. One-yr patient and graft survival rates were 100%. No patients experienced antibody-mediated or cell-mediated rejection. No patients had postoperative infections, and all patients were free of opportunistic infections at one-yr post-transplant. All patients were maintained safely on steroid-free immunosuppression. There were no intraoperative complications. In pediatric end-stage heart and liver disease patients with low immunologic risk, it is reasonable to proceed with en bloc CHLT so long as there is an experienced surgeon to perform the case. This offers operative and immunologic advantages to the recipient while maintaining equivalent, if not improved, recipient and graft outcomes.

Abstract

Favorable outcomes in Ebstein's anomaly are predicated on tricuspid valve competence and right ventricular function. Successful valve repair should be aggressively pursued to avoid the morbidity of prosthetic tricuspid valve replacement. We report our experience with valve-sparing intracardiac repair, emphasizing novel concepts and techniques of valve repair supplemented by selective bidirectional Glenn (BDG).Between June 1993 and December 2008, 57 nonneonatal patients underwent Ebstein's anomaly repairs. The median age at operation was 8.1 years. All were symptomatic in New York Heart Association (NYHA) functional class II (n = 38), III (n = 17), or IV (n = 1). Preoperatively, 26 had mild or moderate cyanosis at rest. We used a number of valve reconstructive techniques that differed substantially from those currently described. BDG was performed in 31 patients (55%) who met specific criteria.No early or late deaths occurred. At the initial repair, 3 patients received a prosthetic valve. Four patients required reoperation for severe tricuspid regurgitation. Repeat repairs were successful in 2 patients. At follow-up (range, 3 months to 6 years), all patients were acyanotic and in NYHA class I. Tricuspid regurgitation was mild or less in 49 (86%) and moderate in 6 (11%). Freedom from a prosthesis was 91% (52 of 57).Following a protocol using BDG for ventricular unloading in selected patients with Ebstein's anomaly can achieve a durable valve-sparing repair using the techniques described. Excellent functional midterm outcomes can be obtained with a selective one and a half ventricle approach to Ebstein's anomaly.

Abstract

Total cavopulmonary connection (CPC) has a significant incidence of late failure due to increased systemic venous pressure and low cardiac output. Mechanical support could prevent failure by correcting hemodynamics. We established a model of inferior CPC using an axial flow pump (Thoratec HeartMate II, Thoratec Corp. Pleasanton, CA) in a group of ten 47-57 kg sheep and assessed hemodynamics and metabolism as a potential chronic treatment option for failed Fontan circulation. After pilot studies (n = 7), three animals underwent pump-supported inferior CPC to assess hemodynamic and metabolic responses. Pump inflow was connected to the inferior vena cava (IVC) and outflow to the main pulmonary artery. The IVC was ligated at the right atrium. Hemodynamic and biochemical parameters were recorded over four days. The first seven animals died from pump-related causes (graft kinking, three; pump thrombosis, one) or other causes (GI bleeding, one; suspected stroke, two). The subsequent three animals were electively euthanized on postoperative day four due to IRB requirements. Over the four day postoperative period, pump flow was 3.43 +/- 0.62 L/min and IVC pressure 4.05 +/- 3.21 mm Hg (mean +/- SD). Lactate levels remained normal. Low pressure and high-volume IVC flow was sustained by mechanical support. We will next attempt chronic pump implantation.